The objectives of this current planning grant are to establish the ICMIC organizational and operational infrastructure and to develop new multidisciplinary research projects. The organizational structure will consist of investigators with different technical and research interests and expertise in order to foster a significant cross-fertilization of ideas and concepts. This "brainstorming" approach has already yielded the identification of very promising and novel imaging applications. The overall approach we are taking will be to develop and test new molecular constructs that will activate reporter genes detectable by either PET or bioluminescence imaging to "report" the occurrence of specific cellular or molecular events. These events include apoptosis, p53 mutation, DNA damage, immune response, angiogenesis and therapeutic intervention. Both the initial biological event and the subsequent measured biological response (e.g. tumor cellularity/cell kill, tumor perfusion, biochemical alterations, etc.) will be noninvasively monitored in vivo. This approach will provide for a more complete understanding of the events involved in the transformation process leading to tumor initiation, progression, angiogenesis, metastasis, immune response, and response to therapy. The development of additional molecular reporter constructs is anticipated and will be made available to both the internal and external research community in an effort to foster productive interdisciplinary and unique collaborations in cancer research based upon new molecular imaging capabilities. These exciting capabilities should serve to foster new ideas in both basic biology and in therapeutic intervention. A Small Animal Tumor Imaging Resource has been developed and was recently funded by the NIH/NCI as part of the University of Michigan Comprehensive Cancer Center. This Center houses 2T and 7T horizontal bore MRI/S systems, an in vivo bioluminescent imaging system, a microCT scanner and autoradiograpkic and digital image processing cores. We propose to use this resource as a foundation for establishing an In Vivo Cellular and Molecular Imaging Center (ICMIC) at the University of Michigan. The institution has committed additional resources to assist with the establishment of the ICMIC in the form of additional imaging capabilities including a new 9.4T MRI system with microimaging capabilities and a MicroPET system. A vital aspect of planning this ICMIC is that the University of Michigan will have a unique advantage of having all of these multimodality imaging capabilities contained within a single infrastructure which will allow greater accessibility and cross-modality comparisons for cancer researchers independent of departmental affiliation.